Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung.

Abstract

Secretory leukocyte proteinase inhibitor (SLPI) and alpha1-proteinase inhibitor (alpha1(PI)) cannot fully explain the total neutrophil elastase (NE) inhibitory capacity detected in bronchoalveolar lavage (BAL) fluid, suggesting the existence of other NE inhibitor(s). In the present study, we measured the concentrations of elafin, a newly described, low-molecular-weight serine proteinase inhibitor, SLPI, and alpha1(PI) in BAL fluids from eight healthy subjects, 13 asymptomatic farmers, seven farmers with active farmer's lung (FL), and seven farmers with previous (Ex) FL. In addition to SLPI and alpha1(PI), elafin was present in BAL fluids from control subjects and asymptomatic farmers, 13 (7-31) and 12 (7-67) mmol/mol of albumin (median and range) respectively. Elafin concentration increased significantly to 105 (38-207) mmol/mol of albumin in farmers with active FL and was also elevated in farmers with Ex FL. Elafin levels were highly correlated with lung inflammatory cell numbers, especially lymphocytes, and the decrease in single-breath diffusion capacity (DLCO). Elafin and SLPI were linked to yet uncharacterized proteins in BAL fluids. In conclusion, elafin is a constituent of BAL fluid from normal subjects and is found in enhanced concentrations in FL and in farmers with lymphocytic alveolitis. This suggests that elafin may play a role in lung homeostasis and inflammation.

Human Alveolar Macrophages Express Elafin and Secretory Leukocyte Protease Inhibitor

“…This therm oactinomycete is a causative agent of farmer's lung, a form of hypersensitivity pneumonitis (Corm ier and Schuyler, 1992). Interestingly, we already showed that, in contrast to SLPI, elafin levels are increased in bronchoalveolar lavage fluid of sub jects with this lung disease (Tremblay et al, 1996). This strongly suggests that alveolar macrophages, but not alveolar epithelial cells, are the cellular source of elafin in farm er's lung.…”

“…Elafin and SLPI are two low molecular weight serine protease inhibitors that, together with a r antitrypsin, protect the fragile lung architecture from proteolytic, especially elastolytic, damage (Dijkman, 1995;Tremblay et al, 1996;M cElvaney and Crystal, 1997;Senior and Anthonisen, 1998). While CL}-antitrypsin is mainly synthesized by he patocytes (Perlmutter, 1993) and SLPI is locally produced by airway structural cells (Dijkm an, 1995), the cellular origin of elafin in the lung is yet unknown (Schalkwijk et al, 1999).…”

“…Interest ingly, the expression of elafin and SLPI is dif ferentially regulated in the peripheral lung. For in stance, we have shown that elafin, but not SLPI, is overexpressed in farm er's lung, a form of hyper sensitivity pneumonitis (Tremblay et al, 1996).…”

“…Elafin in alveolar macrophage culture superna tant was m easured with a home-made ELISA as we described previously (Tremblay et al, 1996). SLPI was m easured with an ELISA kit from R& D Systems (Minneapolis, MN, USA).…”

“…Both elafin and SLPI are present in the peri pheral lung where, together with o^-antitrypsin, they contribute to tightly regulate the destructive action of potent proteolytic enzymes, especially neutrophil elastase (Dijkman, 1995;Tremblay et al, 1996;McElvaney and Crystal, 1997;Senior and Anthonisen, 1998). Beside their antiprotease ac tivity, elafin and SLPI are considered as im portant modulators of the host defence and inflammatory response.…”