-transparent.png){kind=logo}
Rabbits given daily intravenous injections of phorbol myristate acetate (PMA) develop acute and chronic pulmonary disease. We distinguished three phases in the histologic progression of the lung injury. An acute phase (occurring within 1.5 hours of the first injection) involved hemorrhagic pneumonitis, increased lung weight, and increased numbers of neutrophils as well as erythrocytes in alveolar fluid. The intermediate phase (occurring 1 to 7 days after the initial injection) involved interstitial pneumonitis: neutrophils and macrophages infiltrated into lung interstitium and alveolar fluid. The relative number of type II alveolar epithelial cells increased dramatically and lung weight became maximal during this phase. In the chronic phase (occurring within 14 days and lasting greater than 77 days) diffuse interstitial fibrosis progressed, whereas inflammatory changes abated. Animals treated daily with PMA developed a linear increase in lung hydroxyproline content beginning on the 7th day of treatment. Values increased to three to four times above controls by day 77. Animals treated with PMA for only 14 days and sacrificed up to 63 days thereafter had lung hydroxyproline values that were intermediate between controls and animals injected daily for 77 days. Their fibrosis neither progressed nor reversed when PMA treatment was stopped. In contrast, animals receiving a single dose of PMA developed only the acute and intermediate phases of injury; no detectable fibrosis occurred, and their lung reactions resolved completely. Finally, animals made neutropenic with nitrogen mustard did not respond to PMA with increased lung weight or changes in alveolar lavage fluid cellularity during the early or intermediate phases of the disease. They did, however, exhibit increased interstitial cellularity. Thus, PMA produces abrupt pneumonitis that progresses to fibrosis. The acute and intermediate phases of injury are neutrophil dependent and reversible, whereas the chronic fibrotic phase is irreversible and requires continued PMA injections for progression.
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
December 1987,
Taiwan yi xue hui za zhi. Journal of the Formosan Medical Association,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
November 1992,
Scandinavian journal of clinical and laboratory investigation,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
December 1988,
The American review of respiratory disease,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
February 1995,
Respiration physiology,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
August 2004,
Clinical and experimental pharmacology & physiology,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
June 1992,
Critical care medicine,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
January 1995,
Journal of drug targeting,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
March 1998,
European journal of pharmacology,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
September 1990,
Journal of the Formosan Medical Association = Taiwan yi zhi,
R G Taylor, and
C E McCall, and
R S Thrall, and
R D Woodruff, and
J T O'Flaherty
November 1980,
Journal of cellular physiology,
