Source: Annual Congress 2002 - Cell biology and genetics of COPD and emphysema
Disease area: Airway diseases

Abstract

How does the airway epithelium adapt to near freezing conditions? We show that calcium-calmodulin kinase II (CAMKII) and Protein kinase C (PKC) combine to ignite ciliary beat frequency (CBF)in the cold. We brushed inferior turbinates (volunteers, 12-45 years) and placed brushings into Medium 199 on ice which stops CBF. Cell viability was confirmed by trypan blue exclusion and cilia were warmed from 4-37[degree]C over 30 min. CBF was measured by our ethically approved blinded protocol (J.Physiol. 496.3, 883-889,96). We tested the hypotheses that PKA/C/CAMKII would regulate the pattern of response of CBF to rising temperature and applied cell permeable inhibitors of their respective catalytic domains (Myr-PKAI, -PKCI and -CAMKI). The phorbol ester PMA (1nM) was used to stimulate PKC (Mwimbi, J.Aerosol.Med,13,273-279,2000) and ionomycin raised cell calcium.
In Medium ±] either Myr-PKAI, MyrPKCI or ionomycin, the onset of CBF remained at 10[degree]C (>30 cells). Myr-CAMKI made cilia beat at 8[degree]C (n=48; p<0.01)but a significant left shift only occurred with Myr-CAMKI + PMA with cilia beating at 4[degree]C with a linear slope maintaining a left shift throughout the thermal range (n=21 cells, p<0.001, regression analysis).
We conclude that singly, neither raising cell calcium, nor PKC/PKA inhibition can ignite CBF at 4[degree]C. However, although inhibition of CAMKII alone can make cilia beat between 8-10 [degree]C, CAMKII inhibition when combined with PKC activation synergistically augments CBF at 4[degree]C, thereafter increasing the slope response of CBF to rising temperature. CBF drives mucus clearance and our work may have implications for the return of airway function in patients exposed to hypothermic shock.
XM thanks the Wellcome/Anonymous & Buist Trusts for support.

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Citations should be made in the following way:
X. Mwimbi, R. Muimo, M. Green, A. Mehta (Dundee, United Kingdom). CAM-kinase II inhibition and protein kinase C activation combine synergistically to initiate ciliary beat frequency despite cellular hypothermia. Eur Respir J 2002; 20: Suppl. 38, 637

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