beta(2) integrins are involved in cytokine responses to whole Gram-positive bacteria

Proinflammatory cytokines have an important pathophysiologic role in septic shock. CD14 is involved in cytokine responses to a number of purified bact erial products, including LPS, However, little is known of monocyte recepto rs involved in cytokine responses to whole bacteria. To identify these rece ptors, human monocytes were pretreated with different mAbs and TNF-alpha wa s measured in culture supernatants after stimulation with whole heat-killed bacteria. Human serum and anti-CD14 Abs significantly increased and decrea sed, respectively, TNF-alpha responses to the Gram-negative Escherichia col i, However, neither treatment influenced responses to any of the Gram-posit ive bacteria tested, including group A and B streptococci, Listeria monocyt ogenes, and Staphylococcus aureus, Complement receptor type III (CR3 or CD1 8/CD11b) Abs prevented TNF-alpha release induced by heat-killed group A or B streptococci, In contrast, the same Abs had no effects when monocytes wer e stimulated with L, monocytogenes or S. aureus, Using either of the latter bacteria, significant inhibition of TNF-alpha release was produced by Abs to CD11c, one of the subunits of CR4, To confirm these blocking Ab data, IL -6 release was measured in CR3-, CR4-, or CD14-transfected Chinese hamster ovary cells after bacterial stimulation. Accordingly, streptococci triggere d moderate IL-6 production (p < 0.05) in CR3 but not CD14 or CR4 transfecta nts. In contrast, L. monocytogenes and S, aureus induced IL-6 release in CR 4 but not CR3 or CD14 transfectants, Collectively our data indicate that be ta(2) integrins, such as CR3 and CR4, may be involved in cytokine responses to Gram-positive bacteria. Moreover, CD14 may play a more important role i n responses to whole Gram-negative bacteria relative to Gram-positive ones.