The role of the polymorphonuclear leukocyte in the pathogenesis of the adult respiratory distress syndrome.

A major nonrespiratory function of the mammalian lung is that of a polymorphonuclear leukocyte reservoir. Within this reservoir, granulocytes are distributed between marginating and circulating pools. Under normal conditions these cells release little, if any, toxic metabolites. Situations which facilitate chemotactic release, activation of complement, or prolonged lowering of pulmonary blood flow lead to sequestration of large numbers of polymorphonuclear leukocytes in the lungs. If these polymorphonuclear leukocytes are then stimulated to release toxic oxygen species, proteases or other metabolites, existing defense mechanisms are overwhelmed and lung injury results. Anaphylatoxins generated by complement activation, humoral factors released from platelets or macrophages, and activation of the kallikrein-kinin and coagulation systems, may exacerbate damage to the alveolar-capillary membrane. Permeability of this membrane increases, there is interstitial and then alveolar edema, with subsequent pulmonary dysfunction. While there is little doubt that this scenario holds true for some experimental models of acute lung injury, its applicability to adult respiratory distress syndrome is still controversial. Nevertheless, adult respiratory distress syndrome does arise under conditions facilitating chemotactic factor release from macrophages (e.g. hyperoxia), in situations where widespread activation of complement occurs (e.g. sepsis, trauma, microemboli), and in shock conditions where pulmonary blood flow is often lowered. Correlations exist between adult respiratory distress syndrome and activation of complement, acute neutropenia, sequestration of polymorphonuclear leukocytes and enhanced functional and metabolic activity of granulocytes. Although these findings suggest that polymorphonuclear leukocytes are an important factor in the pathogenesis of adult respiratory distress syndrome, its precise role remains to be determined.