Cytokine binding to CD4+ inflammatory cells: implications for asthma.
While LCF is present in BAL early after antigen challenge, we know little about its other potential effects beyond CD4+ T cell, monocyte, and eosinophil chemotaxis and monocyte and CD4+ T cell activation. The work described here focuses on the hypothesis that the secreted protein products of T cells participate in the airway inflammatory process that underlies human asthma, and in particular that LCF could play an early role because of the unusual responsiveness of LCF-producing T to histamine. To date, most studies have addressed the measurement of cytokines derived from CD4+ T cells (e.g., IL-2, IL-3, IL-4, IL-5, and GM-CSF) in the airways of asthmatics, and attempted to correlate the presence of protein or mRNA with the complexion of the inflammatory infiltrate. These studies have been based upon the reports that there are increased numbers of CD4+ T cells in the airways of asthmatics, and that the presence of eosinophils might correlate with the secretion of TH2-type cytokines like IL-3, -4, and -5. Using this information as a background, our work has approached the problem in an entirely different way. We have focused our attention on the early events in antigen-induced asthma that are responsible for CD4+ cell accumulation in the lung, including CD4+ T cells, eosinophils, and monocytes. We have attempted to identify mechanisms by which mast cell mediators, in particular histamine, might play a role in the secretion of chemotactic lymphokines that are selective for CD4+ cells by using CD4 itself as a chemotactic factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Center
D M
DM
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118.
Kornfeld
H
H
Wu
M J
MJ
Falvo
M
M
Theodore
A C
AC
Bernardo
J
J
Berman
J S
JS
Cruikshank
W W
WW
Djukanovic
R
R
Teran
L
L
D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001991:Bronchitis / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002630:Chemotactic Factors / Q000032:analysis / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D019410:Interleukin-16; D008222:Lymphokines / Q000032:analysis / Q000378:metabolism; D011485:Protein Binding
D002630:Chemotactic Factors; D016207:Cytokines; D019410:Interleukin-16; D008222:Lymphokines