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Modulation of beta‐glucan‐stimulated respiratory burst in human PMNs by ECM interaction and activation of specific beta‐1 integrins
Author(s) -
O'Brien Xian M,
Lavigne Liz M,
Reichner Jonathan S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1377-b
Subject(s) - integrin , respiratory burst , chemotaxis , fibronectin , chemistry , glucan , phagocytosis , microbiology and biotechnology , antibody opsonization , receptor , peptide , biochemistry , extracellular matrix , biology , opsonin
Invasive fungal infections are a significant cause of morbidity and mortality especially among immunosuppressed patient populations. Transition to a hyphal morphology, not cleared by phagocytosis, correlates with virulence. Our studies show β‐glucan, a component of yeast cell wall, accelerates chemotaxis of human polymorphonuclear leukocytes (PMNs) in a fibronectin (Fn) matrix. β‐glucan activation of the β2 integrin CR3 (αMβ2) via a lectin‐like domain influences PMN regulation of β1 integrins exerting a pro‐chemotactic effect. To examine if β1‐to‐β2 integrin crosstalk affected other PMN functions, β‐glucan was covalently immobilized to a substratum (to prevent uptake) and plasma membrane‐associated respiratory burst was assayed. Immobilized β‐glucan stimulation of reactive oxygen intermediates (ROIs) was dose dependent and CR3 mediated. Fn+β‐glucan suppressed ROIs and decreased adhesion, relieved by a soluble Fn peptide or cyclic RGD peptide. Fn did not inhibit ROIs induced by β‐glucan that could be engulfed or by phorbol esters. β1 integrin activation by immobilized antibodies against α3β1 (VLA3) and α5β1 (VLA5) but no other β1 integrins significantly suppressed β‐glucan induced ROI. Consistently, suppression of the β‐glucan mediated ROI production by Fn is overcome in PMNs pretreated with blocking antibodies to VLA3 or VLA5. These data suggest that activation of VLA3 or VLA5 results in specific receptor cross‐talk to the β2 integrin CR3 to alter PMN innate immune functions. NIH (GM066194) and D.O.E. G.A.A.N.N. grants