Regulation of polymorphonuclear leukocyte cytokine receptor expression: the role of altered oxygen tensions and matrix proteins.
We investigated the effects of hypoxemia +/- reoxygenation (H/R) on matrix protein regulation of polymorphonuclear leukocyte (PMN) IL-1beta types I and II, TNF-alpha (p60, p80), and IL-8R expression compared with normoxic controls. H/R reduction IL-1beta type I, TNF-alpha (p80), and IL-8R expression compared with hypoxic levels. Neither fibronectin nor laminin effected cytokine receptor expression during normoxia, but both fibronectin and laminin significantly reduced IL-1beta type I, TNF-alpha (p80), and IL-8R expression during hypoxia. Following H/R, both fibronectin and laminin significantly reduced IL-1beta type I, TNF-alpha (p80), and IL-8R expression during hypoxia. Following H/R, both fibronectin and laminin significantly increased TNF-alpha (p60, p80) and IL-8R expression. Cross-linking of adherent PMN very late antigen (VLA)-5 and VLA-6 receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8R expression during hypoxia; cross-linking of adherent PMN VLA-5 and and VLA-6 receptors resulted in a progressive increase in TNF-alpha (p60, p80) and IL-8 receptors following H/R. Cross-linkage of IL-1betaR type I, TNF-alphaR (p80), and IL-8R during hypoxia and H/R resulted in increased and subsequently decreased O2- production and degranulation. Inhibition of reduced nicotinamide adenine dinucleotide phosphate oxidase activation with diphenyleneiodonium following hypoxia but before reoxygenation prevented the decreases in IL-1beta types I and II, TNF-alpha (p80), and IL-8R expression that was seen following H/R alone. These results demonstrate that, during hypoxia and H/R, integrin signaling via alpha5beta1, and alpha6beta1 increases and subsequently decreases the expression of PMN cytokine receptors.
Simms
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Rhode Island Hospital/Brown University, School of Medicine, Department of Surgery, Providence 02903, USA.
D'Amico
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D015703:Antigens, CD / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D003432:Cross-Linking Reagents; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D039121:Integrin alpha6beta1; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D023062:Receptors, Interleukin-8A; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D003432:Cross-Linking Reagents; D005353:Fibronectins; D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin; D018121:Receptors, Cytokine; D017469:Receptors, Fibronectin; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D023062:Receptors, Interleukin-8A; D018124:Receptors, Tumor Necrosis Factor; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D010100:Oxygen; D002118:Calcium