Human alveolar macrophage growth factor for fibroblasts. Regulation and partial characterization

P. B. Bitterman, Stephen Israel Rennard, G. W. Hunninghake, R. G. Crystal

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The number of fibroblasts composing the alveolar structures is controlled within narrow limits by a strictly modulated rate of fibroblast replication. One possible source of growth-modulating signals for alveolar fibroblasts is the alveolar macrophage, a member of the mononuclear phagocyte family of cells, which collectively are known to be important sources of growth factors for a variety of target cells. To evaluate the role of alveolar macrophages in the control of alveolar fibroblast replication, macrophages from normal individuals obtained by bronchoalveolar lavage were maintained in suspension culture with and without added stimuli, and supernates were evaluated for fibroblast growth-promoting effect. Supernates from unstimulated macrophages contained no growth factor activity. In marked contrast, supernates from macrophages stimulated with particulates and immune complexes contained a growth factor that caused a significant increase in fibroblast replication rate. Maximum growth factor activity was observed 3-4 hr after macrophage stimulation, at a concentration of 1-2 x 106 macrophages/ml. The alveolar macrophage-derived growth factor eluted from DEAE-cellulose at 0.27 M NaCl at neutral pH had an apparent molecular weight of 18,000, and appeared to be distinct from other characterized growth factors. The alveolar macrophage-derived growth factor stimulated lung fibroblast DNA synthesis within 12 hr, with cell division apparent within 48 hr. In serum-free culture, the alveolar macrophage-derived growth factor by itself did not promote fibroblast replication, but rather acted as a progression factor causing a synergistic increase in fibroblast replication rate in the presence of competence factors such as fibroblast growth factor or platelet-derived factor. These studies suggest that when stimulated, human alveolar macrophages may modulate, in part, the replication rate of alveolar fibroblasts by releasing a growth factor within the alveolar microenvironment.

Original languageEnglish (US)
Pages (from-to)806-822
Number of pages17
JournalJournal of Clinical Investigation
Volume70
Issue number4
DOIs
StatePublished - Jan 1 1982

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Fibroblasts
Intercellular Signaling Peptides and Proteins
Macrophages
Alveolar Macrophages
alveolar macrophage growth factor
DEAE-Cellulose
Fibroblast Growth Factors
Bronchoalveolar Lavage
Phagocytes
Growth
Antigen-Antibody Complex
Cell Division
Mental Competency
Suspensions
Blood Platelets
Molecular Weight
Lung
DNA
Serum

ASJC Scopus subject areas

  • Medicine(all)

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Human alveolar macrophage growth factor for fibroblasts. Regulation and partial characterization. / Bitterman, P. B.; Rennard, Stephen Israel; Hunninghake, G. W.; Crystal, R. G.

In: Journal of Clinical Investigation, Vol. 70, No. 4, 01.01.1982, p. 806-822.

Research output: Contribution to journalArticle

Bitterman, P. B. ; Rennard, Stephen Israel ; Hunninghake, G. W. ; Crystal, R. G. / Human alveolar macrophage growth factor for fibroblasts. Regulation and partial characterization. In: Journal of Clinical Investigation. 1982 ; Vol. 70, No. 4. pp. 806-822.
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