A novel β ₁ ‐dependent adhesion pathway on neutrophils: a mechanism invoked by dihydrocytochalasin B or endothelial transmigration

Abstract

It is generally accepted that the beta 2-integrin is restricted to mononuclear leukocytes. The objective of this study was to determine whether neutrophils can also express beta 1-integrin (specifically alpha 4 beta 1) and whether this can support neutrophil adhesion to endothelial cells and to extracellular matrix. We stimulated neutrophils with dihydrocytochalasin B (DHCB) and various chemotactic stimuli and observed that chemotactic stimuli induced neutrophil adhesion via beta 2-integrin (CD18), whereas DHCB and either fMLP, PAF, or IL-8 induced adhesion to endothelium or protein-coated plastic that was not inhibitable by anti-CD18 antibody. beta 2-integrin-deficient cells, which did not respond to chemotactic stimuli alone, also adhered avidly in the presence of chemotactic stimuli and DHCB. The induced neutrophil adhesion was inhibited by antibody to beta 1- or alpha 4-integrin chains, but only if an anti-beta 2-integrin antibody was also present. Flow cytometry revealed increased expression of both beta 1 and alpha 4 in the presence of fMLP plus DHCB. Transendothelial migration of neutrophils induced by chemotactic stimuli alone also increased expression of beta 1 and alpha 4. Transmigration across deendothelialized membranes induced a similar beta 1 expression on neutrophils suggesting that events other than an endothelial signal elicited beta 1-integrin expression. Transmigration-induced beta 1-dependent expression translated into only modest adhesion to protein-coated plastic. These data suggest that both a pharmacological (DHCB) and a physiological (transmigration) stimulus can invoke expression of alpha 4 and beta 1 on human neutrophils to mediate adhesion.

The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner

“…1,[12][13][14][15][16] Further, the same changes in adhesion molecule expression have previously been reported following stimulation of neutrophils with chemotactic factors in vitro. 23,24 Therefore, using the in situ perfusion system of the rat femoral bone marrow we sought to investigate the functional significance of these changes with respect to the mobilization process.…”

“…23,[29][30][31][32] Expression of CD49d on neutrophils is up-regulated in vivo during specific inflammatory reactions and in vitro when neutrophils migrate in response to chemoattractants. 12,13,23 In this study we report that expression of CD49d is significantly increased as neutrophils are mobilized from the bone marrow. Moreover, we show here, for the first time, that neutrophil mobilization in response to an inflammatory stimulus, MIP-2, is CD49d dependent.…”

Osteoblast retraction induced by adherent neutrophils promotes osteoclast bone resorption: implication for altered bone remodeling in chronic gout

“…Adherent neutrophils express the b 1 integrin CD29/CD49d, and various inflammatory conditions increase neutrophil expression of the subunit CD49d. 14,29,30 Neutrophils also express the b 1 integrin subunit CD49e. 31 CD29 and ICAM-1 were expressed by OBs, while CD49d and CD49e were not ( Table 1).…”

“…Of relevance to this hypothesis, neutrophils express b2 integrins (CD11a-d/CD18) involved in their adhesion and migration, and the b1 integrin CD29/CD49d (also known as b1/a4) in pathophysiological conditions. [13][14][15] OBs also express integrins with potential counter-receptors for neutrophil integrins. 16 The nature of the integrins implicated in the adhesion of neutrophils to human OBs is presently unknown.…”

The α4β1 (Very Late Antigen (VLA)-4, CD49d/CD29) and α5β1 (VLA-5, CD49e/CD29) Integrins Mediate β2 (CD11/CD18) Integrin-Independent Neutrophil Recruitment to Endotoxin-Induced Lung Inflammation

“…Although expressed at low levels on PMNLs, ␣ 4 ␤ 1 and ␣ 9 ␤ 1 have been shown to mediate human PMNL rolling or transendothelial migration in vitro, and ␣ 4 ␤ 1 can contribute to PMNL migration in rat models of inflammation (19,22,24). The ␣ 2 ␤ 1 , ␣ 4 ␤ 1 , ␣ 5 ␤ 1 , ␣ 6 ␤ 1 , and ␣ 9 ␤ 1 integrins may also mediate extravascular migration of PMNL (17,20,22).…”