Human C-reactive protein inhibits neutrophil chemotaxis in vitro: possible implications for the adult respiratory distress syndrome.
C-reactive protein (CRP) is an acute-phase protein whose serum concentration can rise dramatically after onset of inflammation. Although the precise physiologic role of elevated CRP is not known, in vitro studies have shown that CRP potentially has both pro- and anti-inflammatory properties. We hypothesized that an elevation in serum CRP may be a mechanism to control acute inflammation by down-regulating some neutrophil functions. Therefore, elevated serum CRP levels in an inflammatory state in the lung, such as the adult respiratory distress syndrome (ARDS), may have a protective effect. We observed that highly purified CRP, at levels greater than 25 micrograms/ml, inhibited both random neutrophil movement and C5a-induced chemotaxis. Neutrophils incubated with CRP showed a dose-dependent diminution of migration toward chemotactic stimuli, with complete inhibition occurring at 100 micrograms/ml. This inhibitory effect of CRP on neutrophil movement was only partially reversed by washing the CRP-treated cells before assaying their chemotactic movement to 1 nmol/L C5a. Next we examined the neutrophil chemotactic activity of serum collected from normal nonsmokers, from patients at high risk for developing ARDS, and patients with ARDS. Both high-risk and ARDS serums has significantly less (p less than 0.001) neutrophil chemotactic activity than serums from normal subjects. In addition, serums from high-risk and ARDS patients had significantly elevated (p less than 0.001) levels of CRP compared with normal subjects. Anti-CRP treatment of ARDS and high-risk serum samples resulted in a significant increase (p less than 0.05) in the neutrophil chemotactic activity. Finally, addition of highly purified CRP to normal serum significantly reduces its neutrophil chemotactic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Kew
R R
RR
Department of Internal Medicine, St. Louis University School of Medicine, MO.
Hyers
T M
TM
Webster
R O
RO
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011379:Prognosis; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000276:immunology*; D012307:Risk Factors
D002097:C-Reactive Protein