ALVEOLAR MACROPHAGES OF PATIENTS WITH ADULT-RESPIRATORY-DISTRESS-SYNDROME EXPRESS HIGH-LEVELS OF HEAT-SHOCK-PROTEIN-72 MESSENGER-RNA

Adult respiratory distress syndrome (ARDS), a multifactorial disease w ith poor prognosis, is characterized by an accumulation of inflammator y cells within the airspaces of the lungs. There is evidence that alve olar macrophages (AM) are involved in the pathogenesis of this pulmona ry disease, It has been demonstrated that AM synthesize heat shock pro teins (HSPs) after exposure to certain stress factors. Increasing evid ence suggests that HSPs could confer protection against oxidative inju ry, noxious molecules, and bacterial toxins. In stressed cells HSP 72 appears to be essential for survival during and after exposure to cell ular injury. The aim of this study was to evaluate the magnitude of HS P 72 expression by human AM of patients with ARDS and correlate that w ith respiratory burst activity. Bronchoalveolar lavage was performed i n six ARDS patients, 10 patients with high risk for developing ARDS, a nd two patients who underwent bronchoscopy for other reasons. Spontane ous ex vivo expression of HSP 72 in AM could be demonstrated by immuno cytochemistry. Total RNA as well as poly(A)-rich mRNA were extracted f rom recovered AM and analyzed by Northern blot and slot blot using a h uman HSP 72-specific probe. Signals of slot blot were analyzed by dens itometry and expressed as relative levels of HSP 72 mRNA of stressed ( 42 degrees C) HT 1080 control cells. Significantly (p < .001) higher l evels of HSP 72 mRNA were measured in patients with ARDS (96.2 +/- 9.5 relative levels) in comparison to those not developing this syndrome (46.0 +/- 4.2). With regard to respiratory burst activity of AM in pat ients with ARDS, there was a negative correlation between HSP 72 expre ssion and reactive oxygen species production. The AM of patients with ARDS with high relative levels of HSP 72 expression showed low respira tory burst activity. A predictive value for disease severity of high l evel of HSP 72 mRNA in AM in patients at risk for ARDS has to be evalu ated by future studies. This demonstration of HSP 72 expression ex viv o suggests a protective role of HSP response against endo/exogenously generated stress factors in AM.