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Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravityInflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.
Document ID
Document Type
Reprint (Version printed in journal)
Sundaresan, Alamelu
(Wyle Laboratories, Life Sciences-Systems & Services Houston, Texas 77058, United States)
Risin, Diana
Pellis, Neal R.
McIntire, L. V.
Date Acquired
August 21, 2013
Publication Date
February 1, 2002
Publication Information
Publication: In vitro cellular & developmental biology. Animal
Volume: 38
Issue: 2
ISSN: 1071-2690
Subject Category
Life Sciences (General)
Distribution Limits
NASA Discipline Cell Biology
Non-NASA Center

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