HETEROGENEITY OF TYPE-III PROCOLLAGEN N-TERMINAL PEPTIDES IN BAL FLUID FROM NORMAL AND FIBROTIC LUNGS

Levels of the N-terminal propeptide of type III collagen (PIIINP) in b ronchoalveolar lavage fluid (BALF) are thought to reflect type III col lagen production by the lungs, and increased levels have been reported in patients with pulmonary fibrosis. We wanted to know more about the relative proportions of these peptides in normal BALF, whether they a ltered in pulmonary fibrosis, and whether lymphoid tissue is capable o f clearing PIIINPs. In this study, we used a radioimmunoassay which de tects the different forms of PIIINP-related antigens with equal specif icity, to measure PIIINPs in serum and BALF of patients with cryptogen ic fibrosing alveolitis (CFA). To investigate why PIIINP profiles in B ALF differed from serum, the absolute concentration and relative propo rtion of PIIINPs in lymph afferent and efferent to the popliteal lymph node of a sheep were also determined. PIIINP concentrations were sign ificantly greater in serum and BALF of patients with CFA, compared wit h controls. Gel chromatography indicated that serum antigen distributi on, both of patients and controls, contained approximately 20% Col 1-3 ; the remainder being Col 1. In contrast, BALF contained Col 1-3 and C ol 1, together with an antigen of high molecular weight (>150 kD). The relative proportion of each antigen varied quite widely, but there we re no apparent differences between patients and controls. The concentr ation of PIIINPs in afferent lymph was 295 ng.ml-1 and in efferent lym ph was 104 ng.ml-1. Gel chromatography demonstrated that a significant amount of Col 1-3, together with a high molecular weight peptide, had been cleared during passage through the node. We conclude that BALF c ontains a heterogeneity of PIIINPs, and that processes other than type III collagen production may affect total concentrations of PIIINPs in BALF. Clearance of Col 1-3 and higher molecular weight moieties by ly mphoid tissue may account for the differences in PIIINPs between BALF and serum.