Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.

Abstract

Abstract. Human polymorphonuclear leukocytes (PMN) released large quantities of hydrogen peroxide in response to tumor necrosis factor, but only when the cells were adherent to surfaces coated with extracellular matrix proteins. The PMN did not respond when exposed to cytokines and matrix proteins in suspension, or when exposed to cytokines while adherent to surfaces coated with stearic acid. PMN from children with genetic deficiency of the CDll/CD18 integrins underwent a normal respiratory burst upon adherence to uncoated polystyrene, but not in response to tumor necrosis factor when tested on polystyrene that was coated with serum, fibronectin, vitronectin, fibrinogen, thrombospondin, or laminin. Anti-CD18 antibodies, alone of sixteen antibodies tested, induced a similar defect in PMN from normal donors, when the PMN were tested on surfaces coated with serum, fibrinogen, thrombospondin, or laminin; no defect was induced by the anti-CD18 monoclonal antibody IB4 in normal PMN tested on surfaces coated with fibronectin or vitronectin. Thus, for cytokines to induce a respiratory burst in PMN, the cells must be able to use CDll/CD18 integrins and must interact with matrix proteins in the solid phase. CDll/CD18, which is already known to serve as a receptor for fibrinogen, may also be a receptor for thrombospondin and laminin. Finally, receptor(s) exist on PMN for fibronectin and vitronectin which are not blocked by the anti-CD18 antibody IB4 but which are nonetheless CDll/CD18 dependent.

Critical role for complement receptor 3 (CD11b/CD18), but not for Fc receptors, in killing of Streptococcus pyogenes by neutrophils in human immune serum

“…These conditions do not readily translate to the ex vivo conditions used here, where simultaneous signaling through other receptors could make the requirement for FcR stimulation redundant. Thus, immobilization of the neutrophils on matrix proteins can induce oxidative burst in neutrophils, particularly in the presence TNF-a [29,30]. Clearly, in the bactericidal assay with growing bacteria there are a number of ways through which such costimulatory pathways can be induced.…”

Human Blood Monocytes Interact with Type I Collagen Through αxβ2 Integrin (CD11c-CD18, gp150-95)

“…A total of 100 l of the Ab solution at the appropriate titer (6 g IgG/ml) was added to 1.5 ϫ 10 6 monocytes in 900 l Dulbecco's solution containing 1.3 mM CaCl 2 and 1 mM MgCl 2 . Microtubes were shaken horizontally at 150 cycles/min for 90 min at 37°C (5,15). Monocyte adhesion and O 2 Ϫ production on collagen I were then evaluated as described above, in the continuous presence of mAbs in the incubation medium.…”

Cytokines in context.

“…IL-6 also induces tissue inhibitor of metalloproteinases in human chondrocytes, synoviocytes and fibroblasts (Lotz and Guerne, 1991 Springer, 1990. (Nathan et al, 1989). TNF-a (Lo et al, 1989) and IL-8 (Detmers et al, 1990) activate/32 integrins so as to promote transient attachment of neutrophils to endothelium, an effect distinct from increased surface expression of the integrins.…”

“…A variety of physiologic peptides, including the cytokine TNF-c~, act as secretagogues for neutrophils, but only if the neutrophils are adherent (Nathan, 1987;Luedke and Humes, 1989) to matrix proteins (Nathan et al, 1989) via/32 integrins (Nathan and Sanchez, 1990;Shappell et al, 1990;Richter et al, 1990). Likewise, the survival of embryonic sensory neurons requires not only brain-derived neurotrophic factor but also laminin (Kalcheim et al, 1987).…”