Am. J. Respir. Cell Mol. Biol., Vol 15, No. 1, 07 1996, 20-34.
Phenotypic analysis of airway eosinophils and lymphocytes in a Th-2- driven murine model of pulmonary inflammation
AD Watkins, CA Hatfield, SF Fidler, GE Winterrowd, JR Brashler, FF Sun, BM Taylor, SL Vonderfecht, GA Conder, ST Holgate, JE Chin and IM Richards
Cell Biology and Inflammation Research, Upjohn Laboratories, Kalamazoo, Michigan, USA.
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.
