Uptake, tissue distribution, and excretion of brevetoxin 3 administered to rats by intratracheal instillation.

Brevetoxins are cyclic polyether neurotoxins produced by the marine dinoflagellate Ptychodiscus brevis. Blooms of P. brevis (red tides) are toxic to fish, marine mammals, and humans. Humans exposed to seaspray aerosols containing brevetoxins may experience respiratory tract irritation. Because a major route of human exposure to brevetoxins is via the respiratory tract, the objective of this study was to examine the toxicokinetics of brevetoxin 3 (PbTx-3) administered to the lung by intratracheal instillation. Twenty-one male F344/Crl BR rats, 12 wk of age, were administered 3H-PbTx-3 (1 microCi, 6.6 microg PbTx-3/kg) by intratracheal instillation. Groups of 3 rats were sacrificed at 0.5, 3, 6, 24, 48, and 96 h after exposure, and tissues were collected. Three additional rats were placed in glass metabolism cages for collection of urine and feces over a 7-d period. PbTx-3-associated activity was cleared rapidly from the lung and distributed throughout the body, chiefly to the carcass, intestines, and liver. Blood, brain, and fat contained the lowest percentages of the administered dose. Although a majority of the PbTx-3 was cleared rapidly from lung, liver, and kidneys, approximately 20% of the initial concentration present in each organ was retained for 7 d. Concentrations of PbTx-3 in brain and fat were low, but remained relatively constant over time. Approximately twice as much PbTx-3-associated activity was excreted in feces than in urine, with the majority of excretion occurring within 48 h after instillation. The results of this study indicate that over 80% of the PbTx-3 is rapidly absorbed from the lung to the blood and distributed to all tissues. The tissues containing the greatest amount of PbTx-3-associated activity reflect the compound's site of deposition, storage compartment, and major route of metabolism and excretion. These results illustrate that brevetoxin exposure by the respiratory route results in systemic distribution of brevetoxin and suggest that the initial respiratory irritation and bronchoconstriction may only be a part of the overall toxicological consequences associated with brevetoxin inhalation.

Fluorescent cytometric analysis of polymorphonuclear leukocytes in Chediak-Higashi syndrome: diminished C3bi receptor expression (OKM1) with normal granular cell density.

Chediak-Higashi Syndrome (CHS) has been associated with recurrent bacterial infections and defective polymorphonuclear (PMN) leukocyte function. Confirmation of the diagnosis of CHS and defective PMN function was established in a 2-month-old with accelerated phase CHS. The diagnosis was confirmed by demonstrating reduced PMN degranulation (beta-glucuronidase release 34.1 +/- 0.9% versus 5.1 +/- 4% and lysozyme release 17.6 +/- 1.2% versus 11.1 +/- 7% (control versus CHS) and staphylococcal bacterial killing at 15' 51.4 +/- 3.6% versus 24.9 +/- .4% (control versus CHS). Additional studies using fluorescent cytometric analysis were made to investigate other etiologies of PMN dysfunction in CHS. Total cell density and PMN granularity, as measured by fluorescent-activated cell sorter side scatter analysis, was no different from CHS and age-matched controls. Although CHS is characterized by large PMN granular inclusions, right angle light scatter analysis in this study suggests that the total cell density within the PMN of patients with CHS is normal (D less than .01). PMN granular release of surface receptors was also studied using antibody binding and fluorescent analysis. OKM1 antibody-binding demonstrated significantly reduced C3bi (MO-1) receptor expression (13% of control) p less than 0.001. Decreased surface reception expression of C3bi receptors may play an additional role in defective PMN mobility, chemotaxis, and bactericidal activity in patients with CHS.