Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Properdin was originally described by Pillemer and co-workers in 1954 as a unique serum protein participating in an alternative pathway of complement (C) activation (1). Over the next several years, the sedimentation behavior of partially purified preparations of properdin was examined in several laboratories and values of 27S, 18S, 10S, and 5-7S were variously reported (1-5). Finally, in 1968 Pensky and co-workers obtained a homogenous preparation of properdin which sedimented at 5.2S in the analytical ultracentrifuge (6). Although earlier discrepancies could be attributed at least in part to methodological limitations, the possibility could not be excluded that the differences might also have been on a more substantive basis, perhaps related to the degree of purification achieved. With the development in our laboratory in 1973 of a radioimmunoassay for the detection of nanogram quantities of properdin (7), sucrose density gradient ultracentrifugation experiments were performed to determine the sedimentation behavior of properdin antigen in normal human serum. Radiolabeled or unlabeled properdin purified to homogeneity according to the method of Pensky et al. (6) served as control. The results, presented in this paper, provide evidence for the existence of multiple sedimenting species of properdin antigen in serum and identify the third component of C (C3) as a constituent of at least one of the heavier sedimenting species.

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