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Modification of surfactant protein D by reactive oxygen‐nitrogen intermediates is accompanied by loss of aggregating activity, in vitro and in vivo
Author(s) -
Matalon Sadis,
Shrestha Kedar,
Kirk Marion,
Waldheuser Stephanie,
McDonald Barbara,
Smith Kelly,
Gao Zhiqian,
Belaaouaj Abderrazzak,
Crouch Erika C.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-120568
Subject(s) - peroxynitrite , reactive nitrogen species , chemistry , nitration , biochemistry , tyrosine , in vivo , reactive oxygen species , collectin , peroxynitrous acid , surfactant protein d , lectin , in vitro , biophysics , innate immune system , biology , superoxide , enzyme , receptor , microbiology and biotechnology , organic chemistry
Surfactant protein D (SP‐D) is an important effector of innate immunity. We have previously shown that SP‐D accumulates at sites of acute bacterial infection and neutrophil infiltration, a setting associated with the release of reactive species such as peroxynitrite. Incubation of native SP‐D or trimeric SP‐D lectin domains (NCRDs) with peroxynitrite resulted in nitration and nondisulfide cross‐linking. Modifications were blocked by peroxynitrite scavengers or pH inactivation of peroxynitrite, and mass spectroscopy confirmed nitration of conserved tyrosine residues within the C‐terminal neck and lectin domains. Mutant NCRDs lacking one or more of the tyrosines allowed us to demonstrate preferential nitration of Tyr314 and the formation of Tyr228‐dependent cross‐links. Although there was no effect of peroxynitrite or tyrosine mutations on lectin activity, incubation of SP‐D dodecamers or murine lavage with peroxynitrite decreased the SP‐D‐dependent aggregation of lipopolysaccharide‐coated beads, supporting our hypothesis that defective aggregation results from abnormal cross‐linking. We also observed nitration, cross‐linking of SP‐D, and a significant decrease inSP‐D‐dependent aggregating activity in the lavage of mice acutely exposed to nitrogen dioxide. Thus, modification of SP‐D by reactive oxygen‐nitrogen species could contribute to alterations in the structure and function of SP‐D at sites of inflammation in vivo.— Matalon, S., Shrestha, K., Kirk, M., Waldheuser, S., McDonald, B., Smith, K., Gao, Z., Belaaouaj, A., Crouch, E. C. Modification of surfactant protein D by reactive oxygen‐nitrogen intermediates is accompanied by loss of aggregating activity, in vitro and in vivo . FASEB J . 23, 1415–1430 (2009)