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Signaling in Human and Murine Lymphocytes in Microgravity: Parallels and ContrastsImmune function in space undergoes dramatic changes, some of which are detrimental to lymphocyte function. These changes may lead to significant immune suppression. Studies with human lymphocytes both in space flight and with ground-based models (NASA in vitro ground-based microgravity analog) indicate that T cell activation is inhibited in microgravity. Other lymphocyte functions, such as locomotion, are also inhibited. There is about an 80 percent homology in the immune response of mice to that of humans. A murine model was investigated because of its ability to parallel some microgravity using hind limb suspension. In in vivo antiorthostatically (AOS)-suspended mice, T cell activation is greatly suppressed, with the majority of activation related cytokines being inhibited. PHA activation in lymphocytes derived from AOS mice (in vivo ground-based microgravity analog) is also suppressed. Calcium ionophore studies in human lymphocytes exposed to modeled microgravity indicate that the calcium pathways are probably unaffected in microgravity. IP3 (inositol triphosphate) receptor expression in both human and mouse lymphocytes cultured in modeled microgravity indicate no suppression of calcium signaling. In the human system, microgravity seems to inhibit signaling cascades either at the level of, or up-stream of, Protein Kinase C (PKC). In particular, a membrane event, such as phospholipase C gamma 1 activity in human lymphocytes is affected, with its direct upstream effector, LAT, being deficiently expressed. In the mouse pathway, LAT is undiminished while another critical intermediate, SLP-76, is diminished significantly. This study identifies critical stages in the human and mouse immune systems and in lymphocytes as a function of microgravity.
Document ID
20060028482
Acquisition Source
Johnson Space Center
Document Type
Conference Paper
Authors
Neal, Pellis
(NASA Johnson Space Center Houston, TX, United States)
Alamelu, Sundaresan
(Universities Space Research Association United States)
Kulkarni, A. D.
(Texas Univ. Health Science Center Houston, TX, United States)
Yamauchi, K.
(Texas Univ. Health Science Center Houston, TX, United States)
Date Acquired
August 23, 2013
Publication Date
January 1, 2006
Subject Category
Life Sciences (General)
Meeting Information
Meeting: 2004 American Society for Gravitational and Space Biology Meeting
Location: New York City, NY
Country: United States
Start Date: November 9, 2004
End Date: November 12, 2004
Sponsors: American Society for Gravitational and Space Biology
Funding Number(s)
OTHER: CDDF Task ID#10723
Distribution Limits
Public
Copyright
Other

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