Phenotypic analysis of airway eosinophils and lymphocytes in a Th-2-driven murine model of pulmonary inflammation.
In order to investigate whether the pulmonary response to helminth antigens mimics that seen in allergic inflammation of the airways, we have examined the phenotypic characteristics of lymphocytes and eosinophils recruited to the airways following Nippostrongylus brasiliensis (N.b.) infection. Specifically, the cellular response was divided into an early and a late phase. During the early response there was a small but significant increase in neutrophil numbers recovered by bronchoalveolar lavage (BAL). Phenotypic analysis of BAL leukocytes revealed an early rise in the percentage of BAL lymphocytes expressing the naive T cell markers CD45RB and L-selectin, and the activation marker IL-2R. In addition, during the early response, there was an increased percentage of lymphocytes expressing the gamma delta TCR, but not the alpha beta TCR. In contrast, the late response was marked by a much larger accumulation, in the lungs and BAL, of memory CD4+ T lymphocytes and an influx of small, hypodense eosinophils which produced LTB4 and LTC4 on stimulation with calcium ionophore. At this time there was a substantial increase in the number of T lymphocytes and eosinophils expressing ICAM-1 and the integrins VLA-4 and LFA-1, implicating these adhesion molecules in inflammatory cell recruitment to the airways. We conclude that the pattern and phenotypic characteristics of the cellular recruitment seen following N.b. infection resemble those seen in early- and late-phase allergic inflammation of the airways in asthma, and therefore N.b. may be used to model these aspects of the disease.
Watkins
A D
AD
Cell Biology and Inflammation Research, Upjohn Laboratories, Kalamazoo, Michigan, USA.
Hatfield
C A
CA
Fidler
S F
SF
Winterrowd
G E
GE
Brashler
J R
JR
Sun
F F
FF
Taylor
B M
BM
Vonderfecht
S L
SL
Conder
G A
GA
Holgate
S T
ST
Chin
J E
JE
Richards
I M
IM
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000032:analysis; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000096:biosynthesis / Q000276:immunology; D004804:Eosinophils / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009559:Nippostrongylus / Q000276:immunology; D011014:Pneumonia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017206:Strongylida Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000382:microbiology / Q000473:pathology*; D013997:Time Factors
D015815:Cell Adhesion Molecules; D015777:Eicosanoids