CONNECTIVE-TISSUE ACTIVATION .36. THE ORIGIN, VARIETY, DISTRIBUTION, AND BIOLOGIC FATE OF CONNECTIVE-TISSUE ACTIVATING PEPTIDE-III ISOFORMS- CHARACTERISTICS IN PATIENTS WITH RHEUMATIC, RENAL, AND ARTERIAL-DISEASE
Cw. Castor et al., CONNECTIVE-TISSUE ACTIVATION .36. THE ORIGIN, VARIETY, DISTRIBUTION, AND BIOLOGIC FATE OF CONNECTIVE-TISSUE ACTIVATING PEPTIDE-III ISOFORMS- CHARACTERISTICS IN PATIENTS WITH RHEUMATIC, RENAL, AND ARTERIAL-DISEASE, Arthritis and rheumatism, 36(8), 1993, pp. 1142-1153
Objective. To determine the origin, distribution, and biologic fate of
platelet-derived connective tissue activating peptide-III (CTAP-III),
to define the relative amounts of the antigen forms (CTAP-III, beta-t
hromboglobulin [beta-TG], neutrophil activating peptide-2 [NAP-2]) in
plasma of normal persons and those with rheumatic or end-stage renal d
isease, and to define the isoforms of CTAP-III in platelets, plasma, t
ransudates, and tissue deposits. Methods. CTAP-III in plasma was measu
red by enzyme-linked immunosorbent assay, and growth promoting activit
y of CTAP-III isoforms was tested in synovial and peritoneal cell cult
ures by measuring increased synthesis of C-14-glycosaminoglycan (C-14-
GAG) and H-3-DNA. Isolated CTAP-III was characterized by Western blott
ing, microsequencing, and mass spectrometry. Results. CTAP-III was the
primary isoform of this antigen family in normal platelets and platel
et-rich plasma; beta-TG and NAP-2 accounted for < 1% of CTAP-III isofo
rms. Previously undescribed isoforms, i.e., CTAP-III des 1, des 1-2, d
es 1-3, and a phosphate adduct of CTAP-III, were observed in varying a
mounts. Elevated plasma levels of CTAP-III antigen were found in a sub
stantial fraction of rheumatic disease patients: 24% of those with rhe
umatoid arthritis, 36% of those with systemic sclerosis, and 15% of th
ose with systemic lupus erythematosus. All 10 patients with end-stage
kidney disease had marked elevations of plasma CTAP-III levels, which
stimulated DNA and GAG synthesis by peritoneal cells in culture. Only
large isoforms (such as CTAP-III) were detected in venous plasma of no
rmal subjects, rheumatic disease patients, and patients receiving long
-term dialysis. Normal human spleen and kidney contained substantial (
mug/gm) amounts of CTAP-III and traces of an isoform with the electrop
horetic mobility of CTAP-III des 1-15/NAP-2. Liver, lung, and urine co
ntained lesser (ng/gm) amounts of CTAP-III. Conclusion. These data sho
w that, among the 10 known isoforms, intact CTAP-III itself was the ma
jor circulating isoform (>90%), and beta-TG was the most rare (0-1%).
Deposition of CTAP-III in tissues, such as synovium, spleen, and kidne
y, is associated with partial processing to NAP-2-like isoforms and th
e potential to induce neutrophil and fibroblast activation in patients
with rheumatic or end-stage renal disease.