Delayed-type hypersensitivity responses regulate collagen deposition in the lung.
A previous report showed that hamsters immunized by epicutaneous application of 2,4,6-trinitrochloro-1-benzene (TNCB) were susceptible to the development of pulmonary interstitial fibrosis (PIF) if challenged in the lung with the water-soluble form of this hapten 2,4,6-trinitrobenzene sulphonic acid (TNBS). In this study, we investigated the immunological mechanisms that contributed to increased collagen content in the lungs of hapten-immune hamsters after receiving a pulmonary challenge of the sensitizing hapten trinitrophenol (TNP). In order to evaluate the concept that delayed-type hypersensitivity (DTH) reaction modulated their response to TNP in the lung such that it eventuated into PIF, we compared the cutaneous DTH response (48 hr after challenge) with lung collagen deposition (14 days after challenge) in several lines (strains) of hamsters. The inbred LSH strain, was a high responder in the DTH assay to TNP and developed non-resolving PIF in the hapten-immune animals. This is called hapten-immune pulmonary interstitial fibrosis or HIPIF. We also observed that female LSH hamsters were more susceptible to HIPIF induced by TNP than males. On the other hand, age factors influenced DTH and PIF in random-bred LVG hamsters since young hamsters (3 months old) were low responders to TNP and did not develop PIF in the HIPIF model but matured LVG hamsters (retired breeders) possessed DTH reactivity to TNP and subsequently developed PIF. These results suggest that lung collagen deposition in hapten-immune hamster is regulated by T-lymphocyte-mediated immune inflammation (DTH) in the lung and both are dependent on the ability to develop a cutaneous DTH reaction to the hapten. The elucidation of possible mechanisms of DTH-mediated non-granulomatous, non-resolving PIF is important for understanding of the role of environmental chemicals similar in action to haptens in the mediation of skin and lung diseases.
Kimura
R
R
Department of Medicine, University of Miami School of Medicine, FL 33101.
Hu
H
H
Stein-Streilein
J
J
D000375:Aging / Q000276:immunology; D000818:Animals; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D010853:Picryl Chloride / Q000276:immunology; D011658:Pulmonary Fibrosis / Q000276:immunology*; D012737:Sex Factors
D003094:Collagen; D010853:Picryl Chloride