Intercellular adhesion molecule 1 and β2 integrins in C1q-stimulated superoxide production by human neutrophils: An example of a general regulatory mechanism governing acute inflammation
✍ Scribed by Shivraj Tyagi; Anne Nicholson-Weller; Sergei F. Barbashov; Sander W. Tas; Lloyd B. Klickstein
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 178 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Objective:
To investigate the role of intercellular adhesion molecule 1 (icam-1) and beta2 integrins in the production of superoxide (o2-) by c1q-stimulated human polymorphonuclear leukocytes (pmn).
Methods:
Pmn were pretreated with f(ab')2 fragments of monoclonal antibodies (mab) that blocked or did not block beta2 integrin-mediated adhesion. the cells were added to wells coated with c1q, and the production of o2- was monitored kinetically as a color change due to reduction of cytochrome c. in some experiments, c1q was co-immobilized with purified icam-1.
Results:
Blocking mab to the shared beta2 integrin subunit, cd18, completely inhibited the o2- response triggered by immobilized c1q, while blocking mab to the alpha subunits of the beta2 integrins each partially blocked the o2- response. pmn treated with c1q were found to activate the beta2 integrins lymphocyte function-associated antigen 1 and cr3 for binding to icam-1. co-immobilization of icam-1 with c1q cooperatively triggered o2- production by pmn.
Conclusion:
Beta2 integrin binding to an icam provided an essential costimulatory signal for o2-production triggered by c1q in pmn. our findings suggest a model for pmn activation in which 2 stimuli are required for o2- production: a first signal that also activates pmn beta2 integrins, followed by a second, beta2 integrin-mediated signal, which occurs physiologically upon pmn binding to icam-1. the requirement for this dual signal for pmn generation of o2- would serve as a regulatory mechanism to limit the production of o2- to a tissue environment where c1q, or some other stimulus, is colocalized with stromal cells bearing up-regulated icam-1. this mechanism may explain why all tissues can express icam-1 and may explain in part why inhibitors of tumor necrosis factor alpha, a major physiologic stimulus of icam-1 up-regulation, are potent antiinflammatory agents.