A Distinct mRNA Encoding a Soluble Form of ICAM-1 Molecule Expressed in Human Tissues

Wakatsuki, Toru; Kimura, Kotohiko; Kimura, Fumihiro; Shinomiya, Nariyoshi; Ohtsubo, Michihiro; Ishizawa, Minoru; Yamamoto, Mikio

doi:10.3109/15419069509081014

Cited by 61 publications

(52 citation statements)

References 49 publications

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“…Previously, sICAM-1 production through alternative splicing of ICAM-1 transcript has been demonstrated in human tissues (32,37). Using a similar strategy to assess for alternative splicing, we designed primers spanning the juxtamembrane sequence of ICAM-1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…sICAM-1 can be produced as a result of proteolytic cleavage or alternative splicing (4,21,32,36,37). We have reported that sICAM-1 is normally present in the alveolar lining fluid and that AEC in culture spontaneously release significant quantities of sICAM-1 (23).…”

Section: Discussionmentioning

confidence: 99%

“…They demonstrated that the production of calcitonin and calcitonin generelated peptide were products of the same gene but were differentially spliced by cells originating from different tissues. There is evidence that the soluble form of ICAM-1 can be differentially spliced in response to inflammatory stimuli (12,32,37). Giorelli et al (12) demonstrated both mICAM-1 and sICAM-1 splice variants in HUVEC and human blood mononuclear cells.…”

Section: Discussionmentioning

confidence: 99%

“…A soluble form of the molecule, soluble intercellular adhesion molecule-1 (sICAM-1), is found in serum and in the alveolar lining fluid (7,19,23). sICAM-1 may be generated by proteolytic cleavage and/or alternative splicing of mICAM-1 messenger RNA (4,35,37). Like mICAM-1, sICAM-1 interacts with LFA-1/Mac-1 to compete with leukocyte binding to mICAM-1 (36) and to stimulate leukocytes (31).…”

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Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells

Mendez

Morris²,

Wilcoxen³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mendez MP, Morris SB, Wilcoxen S, Du M, Monroy YK, Remmer H, Murphy H, Christensen PJ, Paine III R. Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 294: L807-L814, 2008. First published February 15, 2008 doi:10.1152/ajplung.00398.2007.-Membrane-associated intercellular adhesion molecule-1 (mICAM-1; CD54) is constitutively expressed on the surface of type I alveolar epithelial cells (AEC). Soluble ICAM-1 (sICAM-1) may be produced by proteolytic cleavage of mICAM-1 or by alternative splicing of ICAM-1 mRNA. In contrast to inducible expression seen in most cell types, sICAM-1 is constitutively released by type I AEC and is present in normal alveolar lining fluid. Therefore, we compared the mechanism of sICAM-1 production in primary cultures of two closely juxtaposed cells in the alveolar wall, AEC and pulmonary microvascular endothelial cells (PVEC). AEC, but not PVEC, demonstrated high-level baseline expression of sICAM-1. Stimulation of AEC with TNF␣ or LPS resulted in minimal increase in AEC sICAM-1, whereas PVEC sICAM-1 was briskly induced in response to these signals. AEC sICAM-1 shedding was significantly reduced by treatment with a serine protease inhibitor, but not by cysteine, metalloprotease, or aspartic protease inhibitors. In contrast, none of these inhibitors effected sICAM-1 expression in PVEC. RT-PCR, followed by gel analysis of total RNA, suggests that alternatively spliced fragments are present in both cell types. However, a 16-mer oligopeptide corresponding to the juxtamembrane region of mICAM-1 completely abrogated sICAM-1 shedding in AEC but reduced stimulated PVEC sICAM-1 release by only 20%. Based on these data, we conclude that the predominant mechanism of sICAM-1 production likely differs in the two cell types from opposite sides of the alveolar wall.regulation; mouse; cell culture; CD54 INTERCELLULAR ADHESION MOLECULE-1 (ICAM-1) is an ϳ100-kDa molecule belonging to the immunoglobulin supergene family. The membrane-bound form of this protein (mICAM-1) serves as a counter receptor for the ␤ 2 -integrins, CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1), found on leukocytes. Interactions with mICAM-1 facilitate leukocyte transmigration across the endothelium (34) and over the surface of alveolar epithelial cells (AEC) in the lung (27). A soluble form of the molecule, soluble intercellular adhesion molecule-1 (sICAM-1), is found in serum and in the alveolar lining fluid (7,19,23). sICAM-1 may be generated by proteolytic cleavage and/or alternative splicing of mICAM-1 messenger RNA (4, 35, 37). Like mICAM-1, sICAM-1 interacts with LFA-1/Mac-1 to compete with leukocyte binding to mICAM-1 (36) and to stimulate leukocytes (31).sICAM-1 is normally present in the alveolar lining fluid of humans and mice (7,13,14,16,17,23). We have previously demonstrated that type I AEC are the likely source of sICAM-1 in the alveolar lining fluid and that sICAM-1 is constitutively...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells

Mendez

Morris²,

Wilcoxen³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Indeed, ICAM-1 is known to be upregulated by pro-inflammatory cytokines (Inoue et al, 2011;Turner et al, 2011;Wertheimer et al, 1992). Another pool of sICAM-1, produced by alternative splicing (Wakatsuki et al, 1995), may also exist in the seminiferous epithelium, and this pool may be interfering with ICAM-1-mediated cell adhesion above preleptotene/leptotene spermatocytes (Fig. 7F).…”

Section: Icam-1 In the Testis 5683mentioning

confidence: 99%

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

Xiao

Cheng

Mruk

2012

Journal of Cell Science

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SummaryThe mechanism underlying the movement of preleptotene/leptotene spermatocytes across the blood-testis barrier (BTB) during spermatogenesis is not well understood largely owing to the fact that the BTB, unlike most other blood-tissue barriers, is composed of several co-existing and co-functioning junction types. In the present study, we show that intercellular adhesion molecule-1 [ICAM-1, a Sertoli and germ cell adhesion protein having five immunoglobulin (Ig)-like domains, in addition to transmembrane and cytoplasmic domains] is a regulator of BTB integrity. Initial experiments showed ICAM-1 to co-immunoprecipitate and co-localize with tight junction and basal ectoplasmic specialization proteins such as occludin and N-cadherin, which contribute to BTB function. More importantly, overexpression of ICAM-1 in Sertoli cells in vitro enhanced barrier function when monitored by transepithelial electrical resistance measurements, illustrating that ICAM-1-mediated adhesion can promote BTB integrity. On the other hand, overexpression of a truncated form of ICAM-1 that consisted only of the five Ig-like domains (sICAM-1; this form of ICAM-1 is known to be secreted) elicited an opposite effect when Sertoli cell barrier function was found to be perturbed in vitro; in this case, sICAM-1 overexpression resulted in the downregulation of several BTB constituent proteins, which was probably mediated by Pyk2/p-Pyk2-Y402 and c-Src/pSrc-Y530. These findings were expanded to the in vivo level when BTB function was found to be disrupted following sICAM-1 overexpression. These data illustrate the existence of a unique mechanism in the mammalian testis where ICAM-1 can either positively or negatively regulate BTB function.

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ICAM‐1‐targeted nanocarriers attenuate endothelial release of soluble ICAM‐1, an inflammatory regulator

Manthe

Muro

2017

Bioengineering & Transla Med

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Targeting of drug nanocarriers (NCs) to intercellular adhesion molecule‐1 (ICAM‐1), an endothelial‐surface protein overexpressed in many pathologies, has shown promise for therapeutic delivery into and across this lining. However, due to the role of ICAM‐1 in inflammation, the effects of targeting this receptor need investigation. Since ICAM‐1 binding by natural ligands (leukocyte integrins) results in release of the “soluble ICAM‐1” ectodomain (sICAM‐1), an inflammatory regulator, we investigated the influence of targeting ICAM‐1 with NCs on this process. For this, sICAM‐1 was measured by ELISA from cell‐medium supernatants, after incubation of endothelial cell (EC) monolayers in the absence versus presence of anti‐ICAM NCs. In the absence of NCs, ECs released sICAM‐1 when treated with a pro‐inflammatory cytokine. This was reduced by inhibiting matrix metalloproteinases MMP‐9 or MMP‐2, yet inhibiting both did not render additive effects. Release of sICAM‐1 mainly occurred at the basolateral versus apical side, and both MMP‐9 and MMP‐2 influenced apical release, while basolateral release depended on MMP‐9. Interestingly, anti‐ICAM NCs reduced sICAM‐1 to a greater extent than MMP inhibition, both at the apical and basolateral sides. This effect was enhanced with time, although NCs had been removed after binding to cells, ruling out a “trapping” effect of NCs. Instead, inhibiting anti‐ICAM NC endocytosis counteracted their inhibition on sICAM‐1 release. Hence, anti‐ICAM NCs inhibited sICAM‐1 release by mobilizing ICAM‐1 from the cell‐surface into intracellular vesicles. Since elevated levels of sICAM‐1 associate with numerous diseases, this effect represents a secondary benefit of using ICAM‐1‐targeted NCs for drug delivery.

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A Distinct mRNA Encoding a Soluble Form of ICAM-1 Molecule Expressed in Human Tissues

Cited by 61 publications

References 49 publications

Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells

Disparate mechanisms of sICAM-1 production in the peripheral lung: contrast between alveolar epithelial cells and pulmonary microvascular endothelial cells

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

ICAM‐1‐targeted nanocarriers attenuate endothelial release of soluble ICAM‐1, an inflammatory regulator

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