1H-NMR studies of bovine platelet factor 4: histidine assignments and interactions with heparin

Talpas, Christopher J.; Walz, Daniel A.; Lee, Lana

doi:10.1016/0167-4838(91)99011-g

Cited by 16 publications

(9 citation statements)

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“…Lee and co-workers have assigned the NMR resonances of the two histidines and measured their pK values in the presence and absence of heparin. 32 The change in the pK of His-38 was an order of magnitude larger than that of His-50. This observation further discounts the parallel orientation for heparin, which places heparin more than 14…”

Section: Resultsmentioning

confidence: 94%

A model of the platelet factor 4 complex with heparin

Stuckey¹,

Charles²,

Edwards³

1992

Proteins

101

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A model of heparin bound to bovine platelet factor 4 (BPF4) was completed using a graphically designed heparin molecule and the crystallographic coordinates of the native bovine platelet factor 4 tetramer. The oligosaccharides had a chain length of at least eight disaccharide units with the major repeating disaccharide unit consisting of (1----4)-O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1----4)-(2-deoxy-2-sulfamino-2-D-glucopyranosyl 6-sulfate). Each disaccharide unit carried a -4.0 charge. The structure of BPF4 was solved to 2.6 A resolution with R = 0.237. Each monomer of BPF4 contains an alpha-helix lying across 3 strands of antiparallel beta-sheet. Each helix has four lysines, which have been implicated in heparin binding. These lysine residues are predominantly on one side of the helix and are solvent accessible. Electrostatic calculations performed on the BPF4 tetramer show a ring of strong, positive charge which runs perpendicularly across the helices. Included in this ring of density is His-38, which has been shown by NMR to have a large pKa shift when heparin binds to BPF4. Our model of heparin bound to PF4 has the anionic polysaccharide perpendicular to the alpha-helices, wrapped about the tetramer along the ring of positive charge, and salt linked to all four lysines on the helix of each monomer.

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Section: Resultsmentioning

confidence: 94%

A model of the platelet factor 4 complex with heparin

Stuckey¹,

Charles²,

Edwards³

1992

Proteins

101

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“…It has been shown previously that IL-8 binds endothelial cells, possibly via surface proteoglycans, and it has been suggested that this interaction is important for IL-8-dependent neutrophil migration (Rot, 1992a,b). The C terminus of IL-8 has been implicated in heparin binding (Talpas et al, 1993), and also contains several basic residues. An acidic residue within a HS-binding site might be expected to increase the affinity for IL-8 (Witt and Lander, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…Chemokines such as IL-8 are known to bind to GAG, especially heparin (Talpas et al, 1993), and it has been suggested that heparin-related (heparan sulphate) GAG on endothelial cell surfaces localize and present chemokines to selectin-bound leukocytes (Butcher, 1991). A recent study has demonstrated that chemokines may be bound to cell-surface heparan sulphate in vitro (Huber et al, 1991), while an earlier report suggested that HS-which is present on the endothelial cell surface and in the basement membrane-may promote IL-8-dependent transmigration of neutrophils and thus enhance the activity of IL-8 (Webb et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Binding of interleukin-8 to heparan sulphate enhances cervical maturation in rabbits

Belayet

Kanayama

Khatun

et al. 1999

Molecular Human Reproduction

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Cervical ripening is a cytokine-trigged process with substantial remodelling of the cervical extracellular matrix. Interleukin-8 (IL-8) is an important cytokine in cervical maturation. Glycosaminoglycans are also included in this process, but their role in not clearly understood. The effects of heparan sulphate (HS), hyaluronic acid (HA), IL-8, HS ⍣ IL-8 and HA ⍣ IL-8 on biochemical properties of the cervix were examined in non-pregnant rabbits. The changes in vascular pattern with collagen structure of the cervices and immunohistochemical studies, together with the relative collagen concentrations, were determined. A reduction in relative collagen concentration was significant after HS ⍣ IL-8 , IL-8 and HA ⍣ IL-8 treatment (all P < 0.0001). Gel electrophoresis analysis showed that IL-8 bound preferentially to HS than to HA. Neutrophils were significantly increased in number (P < 0.0001) and located predominantly beneath the glandular epithelium and around the blood vessels after HS ⍣ IL-8 treatment. HS ⍣ IL-8 treatment caused cervices to increase their water content and become oedematous. The collagen fibres were considerably dissociated, the interfibrillar spaces markedly dilated, and the blood vessels notably increased and dilated. We conclude that binding to HS enhances the activity of IL-8 in inducing cervical maturation. Key words: cervical maturation/heparan sulphate/hyaluronic acid/interleukin-8/neutrophil activation IntroductionThe non-pregnant cervix is a fibrous structure which undergoes modifications during pregnancy to allow sufficient softening and growth for the passage of the fetus at birth (Harkness and Harkness, 1959;Friedman, 1980;Calder, 1981;Fitzpatrick, 1981). It is well established that the transformation of the uterine cervix to a soft and compliant structure during pregnancy is crucial for a normal delivery. This ripening process can be explained mainly in terms of connective tissue biology (Huszar and Walsh, 1991). Investigations of the structural alterations of cervical connective tissue during pregnancy and labour have focused predominantly on quantitative changes of the collagen content and the role of collagen-degraded enzymes (Ito et al., 1979;Danforth, 1980;Uldbjerg et al., 1983). However, there are strong indications that other macromolecular components of the cervix, such as proteoglycans (PG), may also be involved (von Maillot et al., 1979;Kitamura et al., 1980). PG are core proteins with covalently attached glycosaminoglycan (GAG) chains (Ruoslahti, 1988). In addition to heparin/ heparan sulphate (HS), chondroitin sulphate/dermatan sulphate, keratan sulphate and hyaluronic acid (HA) have also been isolated from the human cervix (von Maillot et al., 1979;Cabrol et al., 1980;Kitamura et al., 1980;Uldbjerg et al., 1983). A marked increase in the GAG content of the cervix during late pregnancy has been demonstrated in rats, rabbits, sheep and humans (Danforth et al., 1974;Golichowski et al., © European Society of Human Reproduction and Embryology 261 1980; Fosang et al., 1984;Mara...

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“…As shown by NMR spectroscopy and x-ray crystallography, IL-8 and platelet factor 4 have similar three-dimensional structures (8)(9)(10)(11)(12). In solution, shown to form homodimers that consist oftwo antiparallel C-terminal a-helices lying on top of a six-stranded 3-sheet (9,10).…”

mentioning

confidence: 99%

“…Chemokines are cationic and bind heparin. The interaction with heparin and related glycosaminoglycans (GAGs), however, has been thoroughly studied for platelet factor 4 only (4)(5)(6)(7)(8).…”

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confidence: 99%

Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8.

Webb¹,

Ehrengruber²,

Clark‐Lewis³

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

415

282

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The interaction of interleukin 8 (IL-8) with heparin was studied by using synthetic IL-8 analogs with Cand N-terminal truncations. Elimination of the N-terminal region preceding the first cysteine, which constitutes the IL-8 receptor binding site, did not affect the afnity to heparinSepharose. Affinity, however, decreased with progressive truncation at the C terminus, and no binding was observed when the C-terminal a-helix was eliminated. The effect of heparin and other glycosaminoglycans on IL-8 activity was also tested.When IL-8 was applied together with heparan sulfate, neutrophil chemotaxis in vitro was enhanced up to 4-fold, and the stimulus-dependent increase in cytosolic free Ca2+ increased markedly in both rate and peak value. Heparin had a similar effect on the Ca2+ response but did not enhance chemotaxis. The glycosaminoglycans by themselves did not elicit neutrophil responses. Their enhancing effect was restricted to stimulation with IL-8 and was not observed when the unrelated chemoattractant fMet-Ile-Phe-Leu was used as the stimulus. Elastase released from stimulated neutrophils was inhibited by heparin, heparan sulfate, and, to a lesser extent, chondroitin sulfate B, conflrming previous observations. Taken together, these results suggest that heparan sulfate, which is present on the endothelial cell surface and in the basement membrane, may have a dual function in diapedesis, promotion of IL-8-dependent transmigration of neutrophils, and protection of the tissue microenvironment from damage by lytic enzymes released from the migrating cells.

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1H-NMR studies of bovine platelet factor 4: histidine assignments and interactions with heparin

Cited by 16 publications

References 0 publications

A model of the platelet factor 4 complex with heparin

A model of the platelet factor 4 complex with heparin

Binding of interleukin-8 to heparan sulphate enhances cervical maturation in rabbits

Binding to heparan sulfate or heparin enhances neutrophil responses to interleukin 8.

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